Cavernous Neurotomy Causes Hypoxia and Fibrosis in Rat Corpus Cavernosum

Abstract

The etiologies of erectile dysfunction (ED) after nerve-sparing radical prostatectomy have not been clearly elucidated. The aim of this study was to evaluate the effects of cavernous nerve injury on cavernous fibrosis, and to consider measures to prevent irreversible damage to the cavernous tissues. Twenty male Sprague-Dawley rats constituted the study population. The animals were divided into 2 groups; group 1 consisted of sham-operated rats (n = 10), and group 2 consisted of rats that underwent incision of both cavernous nerves (n = 10). Three months later, all rats underwent intracavernous papaverine injection (300 and 600 mg), and intracorporal pressures were recorded. Transforming growth factor-beta(1) (TGF-beta(1)) messenger RNA (mRNA) expression from rat penile tissue was measured using reverse transcriptase-polymerase chain reaction. Hypoxia-inducible factor-1alpha (HIF-1alpha), TGF-beta(1), and collagen I and III protein expressions were determined by Western blot analysis and immunohistochemical staining. Erectile function as studied with intracavernosal papaverine injection and histological analysis of penile cross-sections at 3 months was similar in both groups. TGF-beta(1) mRNA expression, HIF-1alpha, TGF-beta(1), and collagen I and III protein expressions were significantly greater in the neurotomy group. Immunohistochemical staining for TGF-beta(1), HIF-1alpha, and collagen III were qualitatively more positive in the neurotomy group, whereas collagen I staining was similar. This study demonstrates an increase in TGF-beta(1), HIF-1alpha, and collagen III synthesis in rat cavernosal smooth musculature after cavernous neurotomies. In theory, cavernous fibrosis may be reduced by employing various vasoactive agents or interventions that increase oxygenation to the corporal tissues during the postoperative period.

Tadalafil rehabilitation therapy preserves penile size after bilateral nerve sparing radical retropubic prostatectomy

“…Similarly to other studies, they concluded that progressive fibrosis in the corpora cavernosa after radical prostatectomy resulted from denervation and/or an ischemic process (19). Several human and animal studies support the hypothesis of maintaining adequate penile oxygenation by preserving neurovascular bundles and thus erectile function, may play an important role in preventing irreversible penile fibrotic changes (8,14,15). User et al performed a study on postpubertal rats and grouped them according to bilateral or unilateral cavernous nerve transection versus a sham operation (14).…”

“…Potential pathophysiology of ED that may occur after RP has been widely discussed in several studies (13)(14)(15) and there are studies evaluating the penile length changes after RP (7,12,16). The mechanism responsible for the reduction in penile length after RP has not been elucidated.…”

“…They suggested the hypothesis that bilateral injury to the cavernous nerves may induce significant apoptosis of smooth muscle cells particularly in the subtunical area which causes penile fibrosis and abnormality of the veno-occlusive mechanism of the corpus cavernosum. Leungwattanakij et al showed that cavernosal neurotomy was associated with an up regulation of fibrogenic cytokines and collagenization of the corporoa smooth muscle in animal model (15). In many studies it has been postulated that a chronic absence of postoperative erections might lead to cavernosal hypoxia (7,12,16).…”

Proerectile pharmacological prophylaxis following nerve-sparing radical prostatectomy (NSRP)

“…In a recent experimental model, penile tissue from rats undergone bilateral incision of cavernosal nerves 3 months earlier showed a significant overexpression of hypoxia-related substances like TGF-beta and collagen I and III compared with the same tissue from a control group. 18 Using a similar neurogenic ED model, User et al 19 documented a significant apoptosis in the subalbugineal smooth muscle cells following bilateral neurotomy of the rat penis. Histomorphometric studies have shown that when a high proportion of trabecular smooth muscles is replaced by collagen, the cavernoocclusive mechanism is lost with subsequent venogenic ED.…”

The role of vacuum erection devices in penile rehabilitation after radical prostatectomy

“…Sustained hypoxia causes overexpression of transforming growth factor-b 1. 26 This leads to increased synthesis of endothelin-1, which is a constrictor of penile smooth muscle and a profibrotic agent. 27 This fibrosis leads to decreased EF.…”